Rift Valley fever (RVF) is a mosquito-borne zoonotic disease in humans and ruminants that is caused by the Rift Valley fever virus (RVFV), a member of the family Bunyaviridae, genus Phlebovirus. RVFV causes abortion and fetal malformation in sheep, cattle and goat, while it causes acute febrile illness in humans. Some human patients also develop complications such as neurological disorders, blindness, or lethal hemorrhagic fever. RVFV is classified as category A priority pathogen because of the impact on human health and agriculture.
RVFV has a tripartite negative-stranded RNA genome containing a S-, M- and L-genome segment. The S-segment encodes the N and NSs proteins with the NSs protein encoded in an ambisense manner. The M-segment encodes Gn, Gc, 78-kD, and NSm proteins. The L-segment encodes an RNA-dependent RNA polymerase. The MP-12 strain of RVFV (See GenBank accession No. DQ380154 (S segment), DQ380208 (M segment), and DQ375404 (L segment), each of which are incorporated herein by reference) is one of the most promising vaccine candidates for Rift Valley fever, and the only RVFV strain that is excluded from the select agent rule. MP-12 was generated by serial passages of wild-type ZH548 strain in human diploid MRC-5 cells in the presence of the chemical mutagen 5-fluorouracil. MP-12 is attenuated—having mutations in the M- and L-segment, while the S-segment retains virulence by encoding a functional NSs protein. NSs suppresses host transcription, including interferon-beta (INF-β) mRNA synthesis, and promotes degradation of dsRNA dependent protein kinase (PKR).
Hunter et al. described that pregnant ewes inoculated with live-attenuated MP-12 vaccine strain at 28 to 56 days of gestation caused abortion or teratogenic effects (11 out of 75 lambs from 50 vaccinated ewes), including cerebellar hypoplasia, spinal hypoplasia, hydranencephaly, prognathia inferior, brachygnathia inferior, arthrogryposis, scoiliosis, lordosis, kyphosis, or dormed head. To improve the MP-12 vaccine for both veterinary and human use, additional strains, variants, or modifications are needed.